All animals pass through three stages of development: embryo-genesis, growth and development, and senescence. The final stage is commonly recognized as the aging process. That is, it represents those events that add up to a gradual deterioration of the body and mind. A major problem associated with the study of senescence is distinguishing between those traits that are caused by the aging process and those that are caused by disease and illness. Senility used to be thought of as a normal part of the aging process, but scientists now know that it is caused by Alzheimer’s disease and does not affect a large portion of the aging human population. Humans become frail with age, but severe frailty is due to the modern, sedentary lifestyle and not the aging process.
In the absence of disease, the body still ages, but the extent and magnitude of the eventual disabilities are greatly reduced. This gentle form of aging would have been common a thousand years ago when humans were more active and had a leaner diet. Many scientists refer to this as healthy or successful aging, whereas aging that is associated with disease is called normal aging. Unfortunately, this convention is confusing since "normal" often implies healthy. In the discussion that follows, aging in the absence of disease will be referred to as classical aging, and aging that is associated with disease will be called modern aging.
Classical aging
Classical aging may be characterized as a gradual reduction in the functional capacity of the individual without the onset of severe disabilities. People who age in this way remain physically active well into their 80s and 90s.Such people seem rare now, but they represent the condition of the elderly that was likely common hundreds of years ago. This is obscured by the fact that the mean human life span during the Middle Ages was only about 30 years as compared to the current average of more than 70 years. This difference implies that people aged more rapidly during the Middle Ages than they do now, but this is not the case. The short human life span during that period was due primarily to infectious diseases, which killed young and old alike and had nothing to do with the rate at which those people aged.
Modern aging
The modern lifestyle, characterized by lack of exercise, smoking, and the consumption of high-fat foods, has seriously distorted the way humans age. Individuals who age by the classical route remain hearty well into their 80s and 90s, whereas those who take the modern route are frail and racked with multiple disorders by the time they reach their 70th year. The difference between these two modes of aging is profound. Jeanne Calment, who typifies classical aging, lived 47 years beyond the typical North American life span of 75 years.
Critics point out that while Calment lived 122 years, many others who apparently followed the classical route did not. This discrepancy is due to a genetic component that modulates the aging process; long-lived individuals often come from long-lived families. But the full extent of gene penetrance, or the influence of an individual’s genes, has yet to be determined. Are genes responsible for long-lived families, or are such families long-lived because they have a long cultural tradition of eating healthy foods and of getting regular exercise?
In 1987, to clarify the interpretation of aging rates, NIA launched the Biomarkers of Aging Project to identify biological signs, or bio-markers, in human subjects that best characterize the classical aging process. Biomarkers, which include the performance of the cardiovascular system, blood insulin levels, blood pressure, and several other factors, provide a way of estimating an individual’s physiological age.These markers provide a simple way of distinguishing between classical aging and modern aging. If the bio-markers indicate a physiological age of 85 years, but the individual’s chronological age is only 65, then that individual’s rate of aging has been accelerated and is an example of modern aging. On the other hand, if the physiological age is less than or equal to the chronological, then that individual is aging by the classical route.
Note that individuals aging by the classical or modern route share some characteristics: Both may develop osteoporosis, but it is generally much milder with classical aging. Classical and modern aging are both associated with a decline in the levels of certain hormones, but the change in the hormonal environment is believed to be more extreme with modern aging. When it comes to the skin, vision, and hearing, the two modes of aging appear to be very similar.
Some gerontologists, in the hope of further characterizing human aging, have focused their attention on centenarians, individuals who invariably follow the classical pattern of aging. The New England Centenarian Study has observed the following:
1. Centenarians are rarely obese. This is particularly true for men, who are nearly always lean.
BIOMARKERS OF CLASSICAL AGING1
|
BIOMARKER |
CHANGE WITH AGE |
|
Arteries |
Increased rigidity without atherosclerosis |
|
Blood pressure |
Increases |
|
Body fat |
Slight increase |
|
Bones |
Mild osteoporosis |
|
Brain |
Some neurons lost; basic functions remain intact |
|
Cancer |
Some benign tumors |
|
Cholesterol |
Slight Increase |
|
Eyes |
Decreased accommodation, acuity, and color sensitivity |
|
Hearing |
Detection of high frequencies is lost |
|
Heart |
Thickness of ventricular wall increases |
|
Hormones |
Growth hormone, testosterone, estrogen, thyroid hormone, and dehyroepiandrosterone (DHEA)2 decrease; insulin, adrenalin, parathyroid hormone, and vasopressin increase |
|
Immune system |
Slight decrease in T cell activity |
|
Joints |
Mild arthritis |
|
Kidneys |
Mild reduction in urine output |
|
Lungs |
Vital capacity3 declines by about 20 percent |
|
Skin |
Increased wrinkling, and atrophy of sweat glands |
|
Vision |
Ability to focus close up is lost, night vision becomes poor, and the ability to detect moving objects is impaired |
Notes
"’Classical aging occurs in the absence of diseases, such as Alzheimer’s or Parkinson’s disease.
2DHEA is a precursor of the sex hormones, estrogen and testosterone.
3Vital capacity is the maximum amount of air inspired with each breath.
2. A history of smoking is rare.
3. Centenarians are invariably better able to handle stress than the majority of the population.
4. Many centenarians are mentally alert and show no signs of senility or the presence of Alzheimer’s disease.
BIOMARKERS OF MODERN AGING1
|
BIOMARKER |
CHANGE WITH AGE |
|
Arteries |
Increased rigidity with atherosclerosis |
|
Blood pressure |
Large Increase |
|
Body fat |
Large increase |
|
Bones |
Severe osteoporosis |
|
Brain |
Many neurons lost; basic functions may be lost |
|
Cancer |
Benign and malignant tumors |
|
Cholesterol |
Increases greatly |
|
Eyes |
Decreased accommodation, acuity, and color sensitivity |
|
Hearing |
Detection of high frequencies is lost |
|
Heart |
Thickness of ventricular wall increases |
|
Hormones |
Growth hormone, testosterone, estrogen, thyroid hormone, and dehyroepiandrosterone (DHEA)2 decrease; insulin, adrenalin, parathyroid hormone, and vasopressin increase |
|
Immune system |
A decrease in T cell activity |
|
Joints |
Severe, crippling arthritis |
|
Kidneys |
Reduction in urine output |
|
Lungs |
Vital capacity3 declines by about 40 percent |
|
Skin |
Increased wrinkling, and atrophy of sweat glands |
|
Vision |
Ability to focus close up is lost, night vision becomes poor, and the ability to detect moving objects is impaired |
Notes
1Modern aging is associated with several diseases, such as cancer, Alzheimer’s, or Parkinson’s disease.
2DHEA is a precursor of the sex hormones, estrogen and testosterone. 3Vital capacity is the maximum amount of air inspired with each breath.
5. Many centenarian women have a history of bearing children later in life (ages 35 to 40), suggesting that their reproductive system is aging at a lower rate than the general population.
6. Metastatic cancer is relatively rare among this group of people.
7. About 88 percent of centenarians delay or escape the development of cardiac disease, stroke, and diabetes.
8. More than 90 percent of centenarians are functionally independent.
9. Exceptional longevity runs in families.
Aging mosaics
The difference between modern and classical aging suggests that the human population is an aging mosaic, consisting of individuals that age at different rates. Aging mosaics can also be found at the level of the cells and tissues and were implied by the neuroendo-crine theory of the aging process, first proposed in the 1970s. This theory, described at length in the next topic, suggests that the rate at which an individual ages is governed by the hypothalamus. The hypothalamus is assumed to be aging at its own rate, which would be higher than other tissues in the body.
The existence of an aging mosaic, involving cells and tissues, was tested experimentally in the 1980s. A computerized histochemical analysis of intact nuclei was used to determine the rate at which chromatin changes with age in various tissues of the housefly. This analysis indicated that certain neurons in the housefly brain (type II) were aging at the highest rate, followed by muscle, and Malpighi-an tubule (insect kidney). Interestingly, not all of the neurons were aging at the type II rate. Most of the neurons examined were aging at the more leisurely pace observed in the Malpighian tubule.
The existence of aging mosaics is extremely important. At the population level, long-lived individuals can be compared to their short-lived brethren in the hope of identifying the factors that are responsible for the difference, and at the same time shed some light on the nature of the aging process itself. A similar strategy may also be applied at the cellular and tissue levels. Some cells or tissues may age more rapidly than others simply because the body places a greater demand on their time; as a consequence, they are forced to be extremely active and thus burn out more quickly. A common example is the human heart, which has to beat nonstop for the life of the individual. It is not surprising, therefore, that this organ is often the first to go. A second example is the pancreatic i-cell. These cells synthesize insulin, which stimulates the uptake of glucose by all of the cells in the body. This is a very demanding job; so much so, that i-cells often suffer metabolic burnout, resulting in the age-related disease known as type II diabetes.
By studying aging mosaics, gerontologists hope to gain a deeper insight into the process of cellular and tissue senescence. This information will be crucial for the development of therapies designed to slow or reverse the aging process.
